Ch 23 Cancer Genetics Flashcards
what is cancer?
a heterogenous group of disorders characterized by the presence of cells that do not respond to normal cell division
what is a tumor?
a distinct mass of abnormal cells
what is meant when cancer is benign?
tumor cells remain localized
what is meant when cancer is malignant?
tumor cells invade other tissues
what is meant when cancer is metastatic?
tumor cells travel to other sites where they can establish secondary tumors
how can cancer be nongenetic?
- if cancer is inherited, every cell should have cancer, caused by the cancer causing gene
- tumors appear only in some tissues
- tumors often appear when a certain age is reached
what does Knudsen’s proposal suggest about cancer?
cancer is a multistep process that requires several mutations
explain the clonal evolution of tumors
mutations enhance cells’ ability to proliferate and become the most common cells in a clone, allowing the clone to become increasingly rapid in growth and aggressive in proliferation properties
normal cellular gene responsible for normal cell gunction
proto-oncogene
gene that stimulates cell division, leading to tumors forming and cancer
oncogene
are oncogenes dominant or recessive acting? why?
dominant-acting; the amount of gene product produced by one allele is enough to have a stimulatory effect
genes that normally inhibit cell division
tumor-suppressor genes
are tumor-suppressor genes dominant or recessive acting? why?
both copies of the allele must be mutated to remove inhibition
inactivation of remaining wild-type allele of a heterozygote
loss of heterozygosity
appearance of mutant phenotype in individual that is heterozygous for the trait
haploinsuffiency
explain how mutations in (proto)oncogenes can contribute to cancer?
a mutation in a proto-oncogene results in an oncogene that stimulates cell division without normal controls, leading to cell proliferation
explain how mutations in tumor-suppressor genes can contribute to cancer?
a mutation in a tumor-suppressor gene prevents the gene from inhibiting cell division, leading to excessive cell proliferation
what are the roles of CDKs? how are they functional?
CDKs add phosphate groups to other proteins, either activating or inactivating the protein
they are functional only when they are associated with cyclin
what are the roles of cyclin and how do they contribute to the cell cycle?
cyclins associate with CDKs, activating them and making them function. cyclins levels oscillate during the cell cycle, allowing the cell to pass through certain stages
describe the G1-S transition
(what checkpoint? what proteins are involved? how does the cell transition into the next stage?)
retinoblastoma (RB) protein binds to E2F, inactivating it
as cyclins D & E increase in G1, they associate with CDKs and phosphorylate RB, inactivating it, which releases E2F
E2F goes to transcribe products necessary for DNA replication –> S phase
what is the role of the retinoblastoma (RB) protein in the G1-S transition?
RB prevents the cell from passing the G1/S checkpoint by binding E2F and inactivating it
what would happen if there was a mutation in the RB protein?
the RB protein won’t be able to bind and inactivate E2F, therefore cell division is always occurring without normal controls
describe the G2-M transition
inactive MPF (cyclin-B + CDK) is dephosphorylated, and critical levels of active MPF allow cell to enter mitosis and divide
what is the mitosis-promoting factor (MPF) composed of?
cyclin-B and CDK
what occurs when cyclin-B levels increase in G2
increasing cyclin-B concentrations combine with CDKs to form active MPFs, which phosphorylates other proteins that bring about events of mitosis
what happens in metaphase, regard cyclin levels?
cyclin-B is rapidly degraded in metaphase, which lowers the amount of active MPF, bringing about events that end mitosis
what is p53 and what is it regulate?
p53 is a tumor-suppressor gene; regulate an inhibitor of CDK
what would happen if there was a mutation in the p53 gene?
CDK activity would stay constant, causing cell proliferation
programmed cell death
apoptosis
how does apoptosis relate to cancer?
cancer cells usually have defects in cellular components that stimulate apoptosis, and cells that need to die proliferate
how does autophagy relate to cancer?
autophagy allows cancer cells to s
explain how the Ras signal transduction pathway is important in the cell cycle
external growth factors bind to receptors that allow adapter molecules to bind, which link to an inactive Ras protein. Ras binds GTP, activating, and activates a series of steps, resulting in the activation of transcription factors that transcribe genes of the cell cycle
how do mutations in Ras genes contribute to cancer?
mutations in Ras genes produce mutant Ras proteins that are always active and continuously stimulate cell division
how are DNA-repair genes and mechanisms associated with cancer?
defects in DNA-repair genes prevent DNA-repair mechanisms fixing defects in genes that may contribute to cancer
explain how mutations in telomerase expression contribute to cancer?
mutations in telomerase lead to telomerase being constantly expressed in somatic cells, which allows for unlimited cell division
growth of new blood vessels
angiogenesis
how do mutations in genes that promote vascularization contribute to cancer?
tumors need oxygen and nutrients to survive. mutations in genes that promote the growth of new blood vessels allows these tumors to stay and grow
why would a reduction in miRNAs contribute to cancer?
miRNAs are responsible for degrading or inhibiting the translation of mRNA
reduction in miRNAs may allow oncogenes that are normally suppressed to be highly expressed
explain how hypomethylation is associated with cancer
lowered DNA methylation leads to transcription of oncogenes that allow for cancer
explain how hypermethylation is associated with cancer
higher DNA methylation leads to tumor-suppressant genes being inhibited
